Blockage of human T lymphocyte Kv1.3 channels by Pi1, a novel class of scorpion toxin

Using the patch-clamp technique we determined that Pandinus imperator toxin Pi1, a recently described peptide toxin having four disulfide bridges inst ead of the usual three in scorpion toxins, blocked Kv1.3 channels of human T lymphocytes from the extracellular side with a 1:1 stoichiometry. Kv1.3 b lock was instantaneous and removable with toxin-free extracellular solution . The toxin did not influence activation or inactivation of the channels. W e found that Pi1 blocked Kv1.3 with less affinity (K-d = 11.4 nM) than the structurally related three disulfide bridge containing toxins Pi2 (50 pM) a nd Pi3 (0.5 nM). The fourth disulfide bridge in Pi1 had no influence on the channel binding ability of the toxin; the less effective block. was due to differences in amino acid side chain properties at positions 11 and 35. (C ) 2000 Academic Press.